CN102924540A - Preparation method of 2-deoxy-D-glucose - Google Patents
Preparation method of 2-deoxy-D-glucose Download PDFInfo
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Abstract
The invention discloses a preparation method of 2-deoxy-D-glucose, relating to the field of production of active pharmaceutical ingredients. The preparation method comprises the following steps of: a, taking 3, 4, 6-triacetyl glucose alkenes as raw materials, removing acetyl protection groups in the presence of alkalis and then performing benzyl protection to obtain an intermediate I shown as a formula II; b, acid-hydrolyzing the intermediate I obtained in the step a to obtain an intermediate II shown as a formula III; and c, performing hydrogenolysis on the intermediate II obtained in the step b to de-protect and re-crystallizing to obtain the 2-deoxy-D-glucoses shown as a formula I. Compared with the prior art, the preparation method of the 2-deoxy-D-glucoses has the advantages of simple preparation process, easy purification for products, high yield, low cost and the like, and is more beneficial to achieving large-scale industrial production.
Description
Technical field
The present invention relates to the production of raw medicine field, specifically a kind of preparation method of 2-deoxy-D-glucose.
Background technology
Deoxyglucose is a large class glucose-derivative family, and deoxyglucose equal ubiquity in each quasi-microorganism take bacterium and actinomycetes as main, is being brought into play important regulating effect especially in the metabolism of actinomycetes and bacterium.In production practice, use maximum be 2-deoxy-D-glucose (2-Dexoy-D-Glucose, write a Chinese character in simplified form: 2-DG), it be natural metabolic antagonist class microbiotic (Woodward, 1954,
Cancer Res.14:599-605), has multiple physiological and pharmacological effects such as to suppress virus infection, yeast fermentation, pathogenic bacterium and growth of tumour cell.Have the effects such as antiviral, antibiotic, anticancer, anti-epileptic, be used for pre-anti-virus and pathogenic bacterial infection etc., can prevent HSV, HIV, SARS, influenza virus etc. and the microbial transmissible disease of pathogeny (Tidmarsh, 3 Nov.2005 PCT US 05/0245462), be with a wide range of applications in industries such as medicine and makeup.
Can retrieve the preparation method of a lot of 2-deoxy-D-glucoses at Scifinder; such as IN 187908 and CN1800193A from D-acetyl glucosamine alkene through removing protecting group; acid hydrolysis obtains 2-deoxy-D-glucose, although this synthetic route is succinct, yield is not high.
The synthetic method of patent in 2004 (PCT Int.Appl., 2004058786,15 Jul 2004) is from the grape thin malt sugar, goes on foot through three and obtains 2-deoxy-D-glucose, and the method is more loaded down with trivial details, and cost is high.Chinese patent CN 102180914A improves above-mentioned patent, has obtained product by triacetyl grape thin malt sugar through two-step reaction, but in the end a step produces a large amount of inorganic salt, purification difficult.
US Patent No. 2004/185538 has been reported the synthetic method take malt sugar addition halogenation and high-pressure hydrogenation dehalogenation as committed step, but reaction reagent is expensive, does not have actual production to be worth.
Summary of the invention
Technical assignment of the present invention is for above-mentioned the deficiencies in the prior art, provide a kind of structure suc as formula
The preparation method of shown 2-deoxy-D-glucose.The method preparation technology is simple, and purifying products is easy, and yield is high, and cost is low, is a kind of simple and direct and efficient synthetic method is easy to suitability for industrialized production.
Technical assignment of the present invention is realized in the following manner: a kind of structure suc as formula
The preparation method of shown 2-deoxy-D-glucose may further comprise the steps:
A, be raw material with 3,4,6-triacetyl grape thin malt sugar, in the presence of alkali, remove the acetyl protection base; Then carry out benzyl protection, obtain suc as formula
Shown mesosome one (3,4,6-, three-O-benzyl grape thin malt sugar);
B, acid hydrolysis step a gained intermediate one, obtain suc as formula
Shown intermediate two (3,4,6-, three-O-benzyl-D-deoxyglucose);
C, step b gained intermediate two hydrogenolysis go the protection, recrystallization obtain suc as formula
2-deoxy-D-glucose.
Its chemical equation is as follows:
Further:
Among the step a, the amount ratio of alkali and 3,4,6-triacetyl glucose olefinic substance is 0.05～4:1, and described alkali is salt of wormwood, sodium methylate or sodium hydroxide;
The reaction solvent that removes the acetyl protection radical reaction is methyl alcohol, and temperature of reaction is 18～35 ℃, and the reaction times is 1～12 hour;
After 3,4,6-triacetyl grape thin malt sugar was removed the acetyl protection base, take dry DMF as solvent, sodium hydride was alkali, carried out the benzyl protection reaction with bromotoluene or Bian benzyl chloride, and temperature of reaction is-5～5 ℃;
Among the step b, the used acid reagent of acid hydrolysis is hydrochloric acid, sulfuric acid or Hydrogen bromide, and acid reagent and intermediate one molar ratio are 0.1～1:1, and temperature of reaction is 20～100 ℃;
Among the step c, the hydrocarbon solution of intermediate two palladiums is gone protection, and intermediate two is 1:0.05～0.1 with the amount ratio of palladium carbon species, and hydrogen pressure is 40～55psi, and temperature of reaction is 20～35 ℃; Described recrystallization solvent is the mixture of one or more materials in methyl alcohol, ethanol, Virahol and the acetone.
Compared with prior art; method of the present invention uses hydrogenation except behind the benzyl protecting group; recrystallization can obtain 2-deoxy-D-glucose; need not the operations such as resin purification or organic solvent purification; having that purifying products is easy, easy to operate, yield is high, cost is low, environmental protection, be easy to the characteristics such as industrialization, is a kind of simple and direct and efficient synthetic method.
Embodiment
Explain below with specific embodiment the preparation method of 2-deoxy-D-glucose of the present invention being done.
Embodiment one:
A, 3,4, the preparation of 6-three-O-benzyl grape thin malt sugar (intermediate one)
Salt of wormwood (50g, 0.362mol) is added in methyl alcohol (400ml) solution of 3,4,6-triacetyl grape thin malt sugar (55g, 0.202mol), reaction mixture is at room temperature stirred spend the night.Behind the filtering inorganic salt, filtrate is evaporated to dried.Add DMF(400ml) and be cooled to 0 ℃, add sodium hydride (40g, 60% content in batches, 1.000mol), drip bromotoluene (125.7g, 0.735mol) behind the stirring 30min, add and remove ice bath, reaction mixture at room temperature is stirred to reacts completely, TLC follows the tracks of detection.Make mixture be cooled to 0 ℃, slowly add frozen water (1000ml), then add methylene dichloride (800ml), isolate organic layer, the aqueous solution extracts with methylene dichloride (2x300ml).Merge organic phase and wash neutrality with water, then use the salt water washing, and through anhydrous sodium sulfate drying.After elimination siccative and steaming desolventize, use recrystallization from ethyl acetate/petroleum ether, get intermediate one 55.6g.Yield 66%.
It is as follows that product detects data:
1H?NMR?(300?MHz,?CDCl3)?δ?7.32-7.21?(m,?15H),?6.42?(dd,?J?=?6.0?Hz,?J?=?1.1?Hz,?1?H),?4.86?(dd,?J?=?6.0?Hz,?J?=?2.6?Hz,?1?H),?4.81?(d,?J?=?11.3?Hz,?1?H),?4.65-4.53?(m,?1?H),?4.20?(m,?1?H),?4.06?(ddd,?J?=?8.2?Hz,?J?=?4.6?Hz,?J?=?3.2?Hz,?1?H),?3.86?(dd,?J?=?6.2?Hz,?J?=?8.5Hz,?1?H),?3.82?(dd,?J?=?4.8?Hz,?J?=?10.9?Hz,?1?H),?3.76?(dd,?J?=3.0?Hz,?J?=?10.7?Hz,?1?H).?MS?(ESI)?m/z:?417.2?[M+H]+。
B, 3,4, the preparation of 6-three-O-benzyl-D-deoxyglucose (intermediate two)
47% Hydrogen bromide (5ml, 0.029mol) is joined in tetrahydrofuran (THF) (200ml) solution of 3,4,6-, three-O-benzyl grape thin malt sugar (21g, 0.051mol), the gained mixture is at room temperature stirred.After TLC tracking detection reaction is complete, with 5% sodium hydrogen carbonate solution reaction solution is transferred to neutrality, with ethyl acetate (3x150ml) extraction.Merge organic phase and washing to neutral, through anhydrous sodium sulfate drying, after concentrating under reduced pressure desolventizes, use the ethyl acetate/hexane recrystallization, get intermediate two 16.6g.Yield 76%.
It is as follows that product detects data:
1H?NMR?(300?MHz,?CDCl3)?δ?7.37-7.15?(m,?30H),?5.41?(m,?1?H),?4.88?(d,?J?=?10.8?Hz,?1?H),?4.86?(d,?J?=?10.8?Hz,?1?H),?4.77?(m,?1?H),?4.70-4.51?(m,?10?H),?4.06-3.98?(m,?2?H),?3.74-3.59?(m,?5?H),?3.51?(m,?3?H),?3.26?(d,?J?=?6.3Hz,?1H),?2.67?(m,?1?H),?2.38?(ddd,?J?=?12.5?Hz,?J?=?5.1?Hz,?J?=?2.2?Hz,?1H),?2.30?(dd,?J?=?12.8?Hz,?J?=?4.9?Hz,?1H),?1.68?(dd,?J?=?12.5?Hz,?J?=?12.5?Hz,?1H),?1.57?(ddd,?J?=?12.0?Hz,?J?=?12.0?Hz,?J?=?9.6?Hz,?1H).?MS?(ESI)?m/z:?435.2?[M+H]+。
The preparation of C, 2-deoxy-D-glucose
With Pd/C(10%, contain 50% water) (110mg) join in ethanol (100ml) solution of 3,4,6-, three-O-benzyl-D-deoxyglucose (13.1g, 0.030mol).Room temperature reaction is 24 hours under (50psi) hydrogen pressure.Reaction mixture is through diatomite filtration, be evaporated to do after, use the methanol/acetone recrystallization, get target product 3.1g, yield 63%.
It is as follows that product detects data:
1H?NMR?(300?MHz,?D2O)?δ?5.21?(dd,?J?=?2.0?Hz,?J?=9.9?Hz,?1?H),?4.23?(dd,?J?=?3.0?Hz,?J?=?3.2?Hz,?J?=?3.7?Hz,?1?H),?3.90?(dd,?J?=?2.1?Hz,?J?=?12.0?Hz,?1?H),?3.88-3.75?(m,?2?H),?3.64?(dd,?J?=?3.2Hz,?J?=?9.9?Hz,?1?H),?2.15?(ddd,?J?=?2.0?Hz,?J?=?3.7?Hz,?J?=?13.9?Hz,?1?H),?1.89?(ddd,?J?=?3.0?Hz,?J?=?9.9?Hz,?J?=?13.9?Hz,?1?H)。
Embodiment two:
A, 3,4, the preparation of 6-three-O-benzyl grape thin malt sugar (intermediate one)
Sodium hydroxide (8.4g, 0.210mol) is added in methyl alcohol (400ml) solution of 3,4,6-triacetyl grape thin malt sugar (55g, 0.202mol), reaction mixture is at room temperature stirred spend the night.Behind the filtering inorganic salt, filtrate decompression is concentrated into dried.Add DMF(400ml) and be cooled to 0 ℃, add sodium hydride (40g, 60% content in batches, 1.000mol), drip bromotoluene (125.7g, 0.735mol) behind the stirring 30min, add and remove ice bath, reaction mixture at room temperature is stirred to reacts completely, TLC follows the tracks of detection.Make mixture be cooled to 0 ℃, slowly add frozen water (1000ml), then add methylene dichloride (800ml), isolate organic layer, the aqueous solution extracts with methylene dichloride (2x300ml).Merge organic phase and wash neutrality with water, then use the salt water washing, and through anhydrous sodium sulfate drying.After elimination siccative and steaming desolventize, use recrystallization from ethyl acetate/petroleum ether, get intermediate one 51.3g.Yield 61%.
It is as follows that product detects data:
1H?NMR?(300?MHz,?CDCl3)?δ?7.32-7.21?(m,?15H),?6.42?(dd,?J?=?6.0?Hz,?J?=?1.1?Hz,?1?H),?4.86?(dd,?J?=?6.0?Hz,?J?=?2.6?Hz,?1?H),?4.81?(d,?J?=?11.3?Hz,?1?H),?4.65-4.53?(m,?1?H),?4.20?(m,?1?H),?4.06?(ddd,?J?=?8.2?Hz,?J?=?4.6?Hz,?J?=?3.2?Hz,?1?H),?3.86?(dd,?J?=?6.2?Hz,?J?=?8.5Hz,?1?H),?3.82?(dd,?J?=?4.8?Hz,?J?=?10.9?Hz,?1?H),?3.76?(dd,?J?=3.0?Hz,?J?=?10.7?Hz,?1?H).?MS?(ESI)?m/z:?417.2?[M+H]+。
B, 3,4, the preparation of 6-three-O-benzyl-D-deoxyglucose (intermediate two)
37% hydrochloric acid (5ml, 0.051mol) is joined in tetrahydrofuran (THF) (200ml) solution of 3,4,6-, three-O-benzyl grape thin malt sugar (21g, 0.051mol), the gained mixture is at room temperature stirred.After TLC tracking detection reaction is complete, with 5% sodium hydrogen carbonate solution reaction solution is transferred to neutrality, with ethyl acetate (3x150ml) extraction.Merge organic phase and washing to neutral, through dried over sodium sulfate, after desolventizing, use the ethyl acetate/hexane recrystallization, get intermediate two 15.3g.Yield 69.8%.
It is as follows that product detects data:
1H?NMR?(300?MHz,?CDCl3)?δ?7.37-7.15?(m,?30H),?5.41?(m,?1?H),?4.88?(d,?J?=?10.8?Hz,?1?H),?4.86?(d,?J?=?10.8?Hz,?1?H),?4.77?(m,?1?H),?4.70-4.51?(m,?10?H),?4.06-3.98?(m,?2?H),?3.74-3.59?(m,?5?H),?3.51?(m,?3?H),?3.26?(d,?J?=?6.3Hz,?1H),?2.67?(m,?1?H),?2.38?(ddd,?J?=?12.5?Hz,?J?=?5.1?Hz,?J?=?2.2?Hz,?1H),?2.30?(dd,?J?=?12.8?Hz,?J?=?4.9?Hz,?1H),?1.68?(dd,?J?=?12.5?Hz,?J?=?12.5?Hz,?1H),?1.57?(ddd,?J?=?12.0?Hz,?J?=?12.0?Hz,?J?=?9.6?Hz,?1H).?MS?(ESI)?m/z:?435.2?[M+H]+。
The preparation of C, 2-deoxy-D-glucose
With Pd/C(10%, contain 50% water) (110mg) join in ethanol (100ml) solution of 3,4,6-, three-O-benzyl-D-deoxyglucose (13.1g, 0.030mol).Room temperature reaction is 24 hours under (50psi) hydrogen pressure.Reaction mixture is through diatomite filtration, be evaporated to do after, use the methanol/acetone recrystallization, get target product 3.1g, yield 63%.
It is as follows that product detects data:
1H?NMR?(300?MHz,?D2O)?δ?5.21?(dd,?J?=?2.0?Hz,?J?=9.9?Hz,?1?H),?4.23?(dd,?J?=?3.0?Hz,?J?=?3.2?Hz,?J?=?3.7?Hz,?1?H),?3.90?(dd,?J?=?2.1?Hz,?J?=?12.0?Hz,?1?H),?3.88-3.75?(m,?2?H),?3.64?(dd,?J?=?3.2Hz,?J?=?9.9?Hz,?1?H),?2.15?(ddd,?J?=?2.0?Hz,?J?=?3.7?Hz,?J?=?13.9?Hz,?1?H),?1.89?(ddd,?J?=?3.0?Hz,?J?=?9.9?Hz,?J?=?13.9?Hz,?1?H)。
Claims (6)
1. one kind prepares structure suc as formula the method for the 2-deoxy-D-glucose shown in the I:
It is characterized in that the method may further comprise the steps:
A, be raw material with 3,4,6-triacetyl grape thin malt sugar, in the presence of alkali, remove the acetyl protection base; Then carry out benzyl protection, obtain suc as formula
Shown intermediate one;
B, acid hydrolysis step a gained intermediate one, obtain suc as formula
Shown intermediate two;
C, step b gained intermediate two hydrogenolysis go the protection, recrystallization obtain suc as formula
Shown 2-deoxy-D-glucose.
2. the preparation method of the described compound formula of claim 1 I is characterized in that, among the step a, the amount ratio of alkali and 3,4,6-triacetyl glucose olefinic substance is 0.05～4:1, and described alkali is salt of wormwood, sodium methylate or sodium hydroxide.
3. preparation method according to claim 2 is characterized in that, among the step a, the reaction solvent that removes the acetyl protection radical reaction is methyl alcohol, and temperature of reaction is 18～35 ℃, and the reaction times is 1～12 hour.
4. preparation method according to claim 1 is characterized in that, among the step a, and 3; after 4,6-triacetyl grape thin malt sugar is removed the acetyl protection base, take dry DMF as solvent; sodium hydride is alkali, carries out the benzyl protection reaction with bromotoluene or benzyl chloride, and temperature of reaction is-5～5 ℃.
5. preparation method according to claim 1 is characterized in that, among the step b, the used acid reagent of acid hydrolysis is hydrochloric acid, sulfuric acid or Hydrogen bromide, and acid reagent and intermediate one molar ratio are 0.1～1:1, and temperature of reaction is 20～100 ℃.
6. preparation method according to claim 1 is characterized in that, among the step c, the hydrocarbon solution of intermediate two palladiums is gone protection, and intermediate two is 1:0.05～0.1 with the amount ratio of palladium carbon species, and hydrogen pressure is 40～55psi, and temperature of reaction is 20～35 ℃; Described recrystallization solvent is the mixture of one or more materials of methyl alcohol, ethanol, Virahol and acetone.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103694279A (en) * | 2013-12-23 | 2014-04-02 | 江西苏克尔新材料有限公司 | Preparation method of 2-deoxy-L-ribose |
| CN105330704A (en) * | 2015-11-13 | 2016-02-17 | 天津现代职业技术学院 | Preparation method of 2-deoxy-D-glucose |
| CN111056918A (en) * | 2019-12-23 | 2020-04-24 | 上海科利生物医药有限公司 | Preparation method of (S) -1,2, 4-butanetriol |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5128463A (en) * | 1991-01-24 | 1992-07-07 | E. I. Du Pont De Nemours And Company | Process for the preparation of 2-deoxy sugars |
| WO2004058786A1 (en) * | 2002-12-31 | 2004-07-15 | Council Of Scientific And Industrial Research | Process for the synthesis of 2-deoxy-d-glucose |
| CN1800193A (en) * | 2005-12-07 | 2006-07-12 | 江苏汉发贸易发展有限公司 | 2-deoxidized glucose preparation method |
| CN102180914A (en) * | 2011-04-06 | 2011-09-14 | 华东师范大学 | Preparation method of 2-deoxidizing-D-glucose |
-
2012
- 2012-10-22 CN CN201210403345.2A patent/CN102924540B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5128463A (en) * | 1991-01-24 | 1992-07-07 | E. I. Du Pont De Nemours And Company | Process for the preparation of 2-deoxy sugars |
| WO2004058786A1 (en) * | 2002-12-31 | 2004-07-15 | Council Of Scientific And Industrial Research | Process for the synthesis of 2-deoxy-d-glucose |
| CN1800193A (en) * | 2005-12-07 | 2006-07-12 | 江苏汉发贸易发展有限公司 | 2-deoxidized glucose preparation method |
| CN102180914A (en) * | 2011-04-06 | 2011-09-14 | 华东师范大学 | Preparation method of 2-deoxidizing-D-glucose |
Non-Patent Citations (4)
| Title |
|---|
| G.W.J.FLEET,等: "Syntheses of 1, 5-dideoxy-1, 5-imino-D-mannitol from D-mannose and from D-glucose", 《TETRAHEDRON LETTERS》 * |
| M.DEJTER-JUSZYNSKI，等: "Studies on the koenigs-knorr reaction: Part III. A stereoselective synthesis of 2-acetàmido-2-deoxy-6-O-α-L-fucopyranosyl-D-glucose", 《CARBOHYDRATE RESEARCH》 * |
| 岳智洲: "3, 4, 6—三-O-苄基葡萄糖烯的制备", 《科技信息》 * |
| 徐淑周，等: "2-脱氧-D-葡萄糖的合成", 《应用化工》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103694279A (en) * | 2013-12-23 | 2014-04-02 | 江西苏克尔新材料有限公司 | Preparation method of 2-deoxy-L-ribose |
| CN103694279B (en) * | 2013-12-23 | 2015-12-02 | 江西苏克尔新材料有限公司 | A kind of method preparing 2-deoxidation-L-ribose |
| CN105330704A (en) * | 2015-11-13 | 2016-02-17 | 天津现代职业技术学院 | Preparation method of 2-deoxy-D-glucose |
| CN105330704B (en) * | 2015-11-13 | 2019-05-10 | 天津现代职业技术学院 | The preparation method of 2-deoxy-D-glucose |
| CN111056918A (en) * | 2019-12-23 | 2020-04-24 | 上海科利生物医药有限公司 | Preparation method of (S) -1,2, 4-butanetriol |
| CN111056918B (en) * | 2019-12-23 | 2022-10-14 | 上海科利生物医药有限公司 | Preparation method of (S) -1,2,4-butanetriol |
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